There has been an increasing interest in optically active .beta.-amino acids and peptides derived from them. Optically active .beta.-amino acids include a number of naturally occurring substances in the free form with an interesting pharmacological profile. Functionalized .beta.-amino acids are important segments of bioactive molecules. For example, Taxol.TM. contains the phenylisoserine side chain as its key pharmacophore, and compounds of cyclic .beta.-amino acids make up the class of .beta.-lactam antibiotics. Additionally, .beta.-amino acids are components of peptidic natural products with a wide range of biological activity. Peptides consisting of .beta.-amino acids have promising pharmaceutical use as orally active drugs since they are hydrolytically stable. Given the significance of the .beta.-amino acids, development of new methodologies for their synthesis, especially for the stereoselective synthesis of chiral .beta.-amino acids, is important.
Among the strategies for the synthesis of racemic .beta.-amino acids is the conjugate addition of nitrogen nucleophiles to enoates. Other common approaches include diastereoselective additions in which the nitrogen nucleophile or the .alpha.,.beta.-unsaturated substrate is chiral. Typical examples include the Michael type addition of optically active lithium amides to .alpha.,.beta.-unsaturated esters, or additions of amines to chiral .alpha.,.beta.-unsaturated esters. These approaches however, require the use of stoichiometric amounts of expensive optically active reagents which limits their utility. A single example of chiral Lewis acid catalysis in the conjugate addition of amines to enoates has been reported, however, this method proceeds with only low to moderate selectivity (highest ee of 42%).
The current methods for the synthesis of chiral .beta.-amino acids suffer from one or more of a number of disadvantages such as low yields, use of costly reagents, intricate purification steps or low enantiomeric excesses. Accordingly, in view of the potential pharmaceutical utility of .beta.-amino acids and .beta.-peptides there is a continuing need for methods which would permit the efficient, large scale preparation of .beta.-amino acids, especially in optically active form.